Oral Cancer (Squamous Cell Carcinoma of the Oral Cavity)

Risk factors

• Tobacco use (cigarettes, cigars, pipe, smokeless tobacco) — strongest modifiable risk factor
• Heavy alcohol use (synergistic with tobacco)
• Betel nut chewing
• HPV — primarily associated with oropharyngeal SCC (tonsil, base of tongue) rather than true oral cavity SCC, but increasingly relevant
• Sun exposure (lip cancer)
• Premalignant lesions: leukoplakia, erythroplakia, oral lichen planus, submucous fibrosis
• Immunosuppression (transplant, HIV)
• Prior head and neck radiation

Pathophysiology

Chronic mucosal exposure to carcinogens drives a stepwise accumulation of mutations (TP53, CDKN2A, NOTCH1, PIK3CA) through hyperplasia, dysplasia, carcinoma in situ, and invasive carcinoma. Lymphatic spread to cervical nodes is common; the depth of invasion correlates with the risk of nodal metastasis and prognosis.

Clinical presentation

Differential diagnosis

• Aphthous ulcer — Small, painful, round ulcer with white pseudomembrane and erythematous halo; self-limited within 2 weeks
• Traumatic ulcer — History of biting or denture trauma; resolves once the trauma is removed
• Herpetic ulcers — Multiple small vesicles that coalesce; keratinized mucosa primarily; recurrent; vesicular phase distinguishes
• Oral lichen planus — Bilateral lace-like white striae (Wickham) or erosive plaques; chronic and symmetrical; biopsy if atypical or persistent
• Leukoplakia and erythroplakia (premalignant) — Painless white or red mucosal patches that cannot be wiped off; high malignant transformation rate for erythroplakia
• Necrotizing sialometaplasia — Sudden palatal ulcer in a smoker or after dental procedure; benign and self-resolving but mimics SCC histologically
• Salivary gland tumor or minor salivary gland malignancy — Submucosal mass without surface ulceration; biopsy
• Syphilitic chancre or gumma — Painless ulcer; serology (RPR, treponemal tests)

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Suspicious oral lesion<br/>not healed at 2-3 weeks] --> B[Incisional biopsy]
  B --> C{SCC confirmed?}
  C -->|No| D[Treat alternative cause<br/>re-examine 2-4 weeks]
  C -->|Yes| E[CT neck + MRI<br/>+ PET/CT if advanced]
  E --> F{Stage}
  F -->|I-II| G[Surgery ± selective<br/>neck dissection]
  F -->|III-IVA/B| H[Surgery + adjuvant<br/>(chemo)radiation]
  F -->|IVC| I[Systemic therapy<br/>palliative care]
  G --> J[Surveillance per NCCN]
  H --> J

Treatment

Complications

• Locoregional recurrence (highest risk in the first 2 years)
• Second primary head and neck or lung malignancy
• Chronic dysphagia, aspiration, xerostomia after radiation
• Osteoradionecrosis of the mandible
• Disfigurement and speech impairment
• Cervical lymphedema
• Nutritional decline and weight loss

PANCE pearls

• Biopsy any oral lesion that has not healed in 2-3 weeks — do not assume aphthous ulcer.
• The lateral tongue and floor of the mouth are the highest-risk subsites.
• Erythroplakia carries the highest malignant transformation risk of premalignant lesions.
• Refer any persistent neck mass in an adult older than 40 with risk factors for prompt workup — assume metastatic SCC until proven otherwise.
• Tobacco and alcohol cessation reduces second primary risk substantially.

References

• NCCN — NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers (current version)
• AAO-HNS — American Academy of Otolaryngology-Head and Neck Surgery resources on oral cavity malignancy
• AJCC — AJCC Cancer Staging Manual, 8th edition (Amin et al., Springer 2017)